Differentiation antagonizing non-protein coding RNA modulates the proliferation, migration, and angiogenesis of glioma cells by targeting the miR-216a/LGR5 axis and the PI3K/AKT signaling pathway.

Purpose: DANCR plays an important role in various types of cancer. However, its role in gliomas remains unclear. In the present study, we aimed to investigate the mechanism underlying the role of DANCR in gliomas. Methods: DANCR expression was measured by qRT-PCR, and expression of LGR5, PI3K, AKT, and phosphorylated AKT (p-AKT) was detected by western blotting. The combination of miR-216a and DANCR was quantified by Luciferase reporter assays. Proliferation, apoptosis and cell cycle, migration and invasion, and angiogenesis of glioma cells were measured by MTT, flow cytometry, Transwell, and Tube formation assays, respectively. Results: DANCR expression was significantly higher in glioma cells than in normal human astrocytes. Silencing of DANCR inhibited proliferation, migration, invasion, and angiogenesis of glioma cells, promoted apoptosis, blocked the cell cycle at the G1/S transition, and reduced LGR5, PI3K, and p-AKT expression. We identified miR-216a as a direct target of DANCR. Silencing of DANCR in glioma cells increased miR-216a expression. Further, miR-216a suppression increased proliferation, migration, invasion, and angiogenesis and inhibited apoptosis of glioma cells transfected with DANCR-targeting siRNA. In addition, miR-216a suppression compromised inhibition of the G1/S transition caused by DANCR silencing. Furthermore, suppression of miR-216a increased accumulation of LGR5, PI3K, AKT, and p-AKT in glioma cells transfected with DANCR-targeting siRNA. Conclusion: DANCR modulates growth and metastasis by targeting the miR-216a/LGR5 axis and PI3K/AKT signaling pathway.

miR-655-3p inhibits cell migration and invasion by targeting pituitary tumor-transforming 1 in non-small cell lung cancer.

miR-655-3p functions as a tumor suppressor in tumor metastases; however, its role and mechanism in regulating cell migration and invasion of non-small cell lung cancer (NSCLC) remain unclear. Here, we found that miR-655-3p expression was markedly decreased in the NSCLC cell lines A549, NCI-H1650, PC14/b, NCI-H1299, and HPAEpiC compared to levels observed in normal human lung fibroblasts. miR-655-3p overexpression significantly inhibited migration and invasion of A549 and PC14/b cells, and pituitary tumor-transforming 1 (PTTG1) expression was up-regulated in the NSCLC cells. Luciferase reporter assays indicated that PTTG1 was a direct target of miR-655-3p. Additionally, PTTG1 overexpression alleviated the inhibitory effect of miR-655-3p on migration and invasion abilities in A549 and PC14/b cells. In conclusion, miR-655-3p inhibits NSCLC migration and invasion by targeting PTTG1, suggesting that miR-655-3p may serve as a therapeutic target to provide a new approach for the clinical treatment of NSCLC.

Securin promotes migration and invasion via matrix metalloproteinases in glioma cells.

Human securin, encoded by pituitary tumor transforming gene 1, is implicated in several oncogenic processes in the pathogenesis of brain tumors, including glioma. The aim of the present study was to examine the effect of securin on the migration and invasion of glioma cells. The results revealed that the overexpression of securin in glioma LN-229 cells significantly increased the invasion and transmigration abilities. By contrast, these abilities were significantly reduced by the downregulation of securin in glioma U373 cells. Furthermore, the results demonstrated that securin overexpression and downregulation significantly increased and decreased the levels of matrix metalloproteinase 2 and 9, respectively. These findings indicate a promotive role for securin in glioma migration and invasion, which may involve the action of matrix metalloproteinases.

Preventive effect of dexamethasone gelatin sponge on the lumbosacral epidural adhesion.

OBJECTIVE: This study aims to explore the preventive effect of dexamethasone gelatin sponge on the lumbosacral epidural adhesion in the laminectomy. METHODS: A total of 36 Wista rats were divided into A, B, C and D groups randomly. Dexamethasone was not used in group A, Dexamethasone was used in group B, Dexamethasone was not used in group C but covered with gelatin sponge, dexamethasone gelatin sponge was used in group D. 3 rats in each group were sacrificed at 4, 8 and 12 weeks after operation respectively and the wound was opened to observe the dural scar formation and the dura adhesion. Immunohistochemical technique was used for histology observation. The expressions of VEGF and VEGFR2 in the epidural scar and surrounding tissues were detected with western blotting and immunohistochemical methods. RESULTS: According to the Rydell score standard, there were different degree of adhesion formation in A, B and C groups while there was no obvious adhesion formation in D group. It was confirmed that the expressions of VEGF and VEGFR2 in group D were lower than that of the other groups. CONCLUSIONS: Dexamethasone gelatin sponge could significantly reduce the occurrence of epidural scar tissue hyperplasia and adhesion after laminectomy in rats, and its mechanism may be related to the decreased expression of VEGF and VEGFR2.

Association of LIG4 and XRCC4 gene polymorphisms with the risk of human glioma in a Chinese population.

We conducted a case-control study to assess the LIG4 and XRCC4 genes polymorphisms and development of glioma. A case-control study including 162 glioma cases and 324 controls was conducted in a Chinese population. Genotypes of rs10131 and rs1805388 in LIG4 and rs2075685 and rs1805377 in XRCC4 were conducted by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Conditional logistic regression analysis showed that subjects carrying AA genotype of LIG4 rs10131 was associated with increased risk of glioma when compared with GG genotype, and the OR (95% CI) was 3.26 (1.50-7.23). We found that GA+AA of LIG4 rs10131 was associated with increased risk of glioma in those without family history of cancer, and the OR (95% CI) was 1.78 (1.12-2.83). However, no association was found between variants of LIG4 rs1805388, XRCC4 rs2075685 and XRCC4 rs1805377 and development of glioma. In conclusion, our results suggest that LIG4 rs10131 polymorphism in the DNA repair pathways plays an important role in the risk of glioma in a Chinese population.

Evaluating the association of polymorphisms in the HAP1 gene with lung cancer risk: a meta-analysis.

Studies on the relationship of HAP1 polymorphisms (-141 T > G; 1349 T > G) and lung cancer risk to date indicated controversial results. This study was devised to clarify whether the polymorphisms predispose to lung cancer. We searched Embase and PubMed up to March 2014 to identify relevant studies. Data from the eligible studies were independently extracted by two investigators. Pooled odds ratio (OR) was calculated to assess the associations between lung cancer risk and the abovementioned polymorphisms. A total of 15 case-control studies were included in this meta-analysis. Both overall analysis and stratified analysis by ethnicity and smoking status indicated no association between lung cancer risk and the 1349 T > G polymorphism. However, a significantly reduced risk of lung cancer was found among carriers of the GG genotype of the -141 T > G polymorphism, as compared with those of the TT genotype (homozygote model: OR = 0.82, 95% confidence interval (CI) 0.73 to 0.93, P(OR) = 0.002). Likewise, the GG genotype was also found to decrease lung cancer risk compared to the GT + TT genotypes (recessive model: OR = 0.82, 95 % CI 0.73 to 0.92, P(OR) = 0.001). Our meta-analysis suggests that the -141 T > G polymorphism, but not the 1349 T > G polymorphism, may have protective effects for lung cancer.

Relationships of LDLR genetic polymorphisms with cerebral infarction: a meta-analysis.

This meta-analysis was undertaken to identify the relationships between genetic polymorphisms in the LDLR gene and the risk of cerebral infarction. The Web of Science (1945-2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966-2013), EMBASE (1980-2013), CINAHL (1982-2013) and the Chinese Biomedical Database (CBM) (1982-2013) were searched for relevant articles without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios (OR) with their corresponding 95% confidence interval (CI) were calculated. Eight case-control studies with a total of 4,655 patients with cerebral infarction and 15,920 healthy control subjects were included in our meta-analysis. Five common polymorphisms in the LDLR gene were evaluated, including rs11669576 A > T, rs1433099 C > T, rs5925 C > T, rs688 C > T, rs1122608 T > G in the LDLR gene. The results of this meta-analysis revealed that cerebral infarction patients had a higher frequency of LDLR genetic polymorphisms than that of healthy controls (allele model: OR 1.17, 95% CI 1.05-1.30, P = 0.004; dominant model: OR 1.18, 95% CI 1.05-1.33, P = 0.007; homozygous model: OR 1.50, 95% CI 1.03-2.16, P = 0.032; respectively), especially for the rs11669576 A > T, rs1433099 C > T and rs5925 C > T polymorphisms. Among different ethnic subgroups, the results demonstrated positive correlations between LDLR genetic polymorphisms and an increased risk of cerebral infarction among both Asians and Caucasians under the allele and dominant models (all P < 0.05). Our findings indicate that LDLR genetic polymorphisms may be strongly involved in the pathogenesis of cerebral infarction, especially the rs11669576 A > T, rs1433099 C > T, rs5925 C > T polymorphisms.

Human leptin triggers proliferation of A549 cells via blocking endoplasmic reticulum stress-related apoptosis.

Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. Leptin is a pleiotropic hormone with antiapoptotic and proliferative roles involved in several systems. However, there is no known antiapoptotic mechanism of leptin in non-small cell lung cancer (NSCLC). So, we investigated the antiapoptotic mechanism of leptin in NSCLC. Proliferation, apoptosis, and the specific mechanism of leptin-transfected cells were analyzed in this study. Leptin, p-Perk, IRE1, cleaved ATF6, spliced XBP1, eIF2-α, TRAF2, CHOP, and caspase 12 proteins were detected by Western blot, and endoplasmic reticulum (ER) stress-related mRNA was detected by semi-quantitative reverse transcription PCR (RT-PCR). Leptin in A549 and transfected cells inhibited cisplatin-activated ER stress-associated mRNA transcription and activation of proteins. ER stress unfolded protein response (UPR) proteins, PERK and ATF6, were involved in leptin-triggered apoptosis. XBP1 and TRAF2 were increased significantly when treated with cisplatin in A549-siLPT and non-transfected cells. CHOP expression was blocked in A549 and transfected cells (LPT-PeP and LPT-EX cells). In conclusion, leptin can promote the proliferation of A549 cells through blocking ER stress-mediated apoptosis. This blocking is mediated by the p-Perk and ATF6 pathway through blocking activation of CHOP.

[Clinical analysis of microsurgical carotid endarterectomy for carotid stenosis and occlusion].

OBJECTIVE: To evaluate the clinical effects of carotid endarterectomy for carotid stenosis and occlusion. METHODS: From August 2005 to November 2008 moderate and severe carotid stenosis or occlusion were found in 16 patients by Doppler ultrasonography (DUS), MRA, CTA, DSA. The stenosis degree ranged from 60% to 99% in 14 patients and complete occlusion in 2 patients. Twelve patients underwent standard carotid endarterectomy (sCEA) in whom 2 patients were placed carotid shunt and 1 patient underwent carotid patch angioplasty. Four patients underwent eversion carotid endarterectomy (eCEA). All operations were performed by microscope. RESULTS: There was no stroke, transient ischemic attack and mortality perioperatively and during follow-up from 1 month to 3 years. The ICA flow detected by follow-up duplex scan and MRA was unobstructed. The primary cerebral ischemic symptoms were obviously improved or disappeared after operation. The postoperative complications included one case of upper gastrointestinal hemorrhage and one case of hoarseness and bucking, which disappeared after medical treatment. CONCLUSIONS: CEA is an effective way for treating carotid stenosis. Different operative methods and techniques deal with different carotid lesions to achieve better effect. Microsurgical technique is useful for exposure of high ICA bifurcation and avoid effectively cranial nerve injury and other complications.